UniProtKB/Swiss-Prot Q08043: Variant p.Arg523Gln

Alpha-actinin-3
Gene: ACTN3
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Variant information Variant position:

523 The position of the amino-acid change on the UniProtKB canonical protein sequence.
Type of variant:

LB/B The variants are classified into three categories: LP/P, LB/B and US.

LP/P: likely pathogenic or pathogenic.
LB/B: likely benign or benign.
US: uncertain significance

Residue change:

From Arginine (R) to Glutamine (Q) at position 523 (R523Q, p.Arg523Gln). Indicates the amino acid change of the variant. The one-letter and three-letter codes for amino acids used in UniProtKB/Swiss-Prot are those adopted by the commission on Biochemical Nomenclature of the IUPAC-IUB.
Physico-chemical properties:

Change from large size and basic (R) to medium size and polar (Q) The physico-chemical property of the reference and variant residues and the change implicated.
BLOSUM score:

1 The score within a Blosum matrix for the corresponding wild-type to variant amino acid change. The log-odds score measures the logarithm for the ratio of the likelihood of two amino acids appearing by chance. The Blosum62 substitution matrix is used. This substitution matrix contains scores for all possible exchanges of one amino acid with another:

Lowest score: -4 (low probability of substitution).
Highest score: 11 (high probability of substitution).

More information can be found on the following page
Polymorphism:

A common variant at position 577 creates a stop codon at position 577, leading to ACTN3 deficiency (PubMed:10192379). The presence of this variant is not associated with any disease phenotype [MIM:617749] (PubMed:11440986). It has a global frequency of almost 44% in the human population according to the Genome Aggregation Database (gnomAD v4.1.0). It is thought that the variant p.Arg577Ter became more frequent as humans migrated out of Africa into the colder climates of central and northern Europe, as individuals carrying this variant are superior in maintaining core body temperature during cold-water immersion due to changes in skeletal muscle thermogenesis (PubMed:33600773). The variant p.Arg577Ter at the homozygous state is underrepresented in elite sprint/power athletes and overrepresented in endurance athletes, suggesting that ACT3 deficiency increases muscle endurance at the cost of power generation (PubMed:12879365, PubMed:15886711, PubMed:18043716, PubMed:29706347). Additional information on the polymorphism described.
Other resources:

Links to websites of interest for the variant.

Variant rs1671064 [ dbSNP | Ensembl ]

Sequence information Variant position:

523 The position of the amino-acid change on the UniProtKB canonical protein sequence.
Protein sequence length:

901 The length of the canonical sequence.
Location on the sequence:

LTQKRRDALERMEKLLETID R LQLEFARRAAPFNNWLDGAV The residue change on the sequence. Unless the variant is located at the beginning or at the end of the protein sequence, both residues upstream (20) and downstream (20) of the variant will be shown.
Residue conservation:

The multiple alignment of the region surrounding the variant against various orthologous sequences.

Human                         LTQKRRDALERMEKLLETIDRLQLEFARRAAPFNNWLDGAV

Mouse                         LTQKRRDALERMEKLLETIDQLQLEFARRAAPFNNWLDGAI

Bovine                        LTQKRRDALERMEKLLETIDQLQLEFARRAAPFNNWLDGAV

Sequence annotation in neighborhood:

The regions or sites of interest surrounding the variant. In general the features listed are posttranslational modifications, binding sites, enzyme active sites, local secondary structure or other characteristics reported in the cited references. The "Sequence annotation in neighborhood" lines have a fixed format:

Type: the type of sequence feature.
Positions: endpoints of the sequence feature.
Description: contains additional information about the feature.

Type	Positions	Description
Chain	1 – 901	Alpha-actinin-3
Repeat	523 – 634	Spectrin 3

Literature citations
Cloning and characterization of two human skeletal muscle alpha-actinin genes located on chromosomes 1 and 11.
Beggs A.H.; Byers T.J.; Knoll J.H.M.; Boyce F.M.; Bruns G.A.P.; Kunkel L.M.;
J. Biol. Chem. 267:9281-9288(1992)
Cited for: NUCLEOTIDE SEQUENCE [MRNA]; VARIANTS GLN-523; ARG-628 AND ARG-776; The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC).
The MGC Project Team;
Genome Res. 14:2121-2127(2004)
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]; VARIANTS GLN-523; ARG-628 AND ARG-776; A common nonsense mutation results in alpha-actinin-3 deficiency in the general population.
North K.N.; Yang N.; Wattanasirichaigoon D.; Mills M.; Easteal S.; Beggs A.H.;
Nat. Genet. 21:353-354(1999)
Cited for: VARIANTS GLN-523 AND 577-ARG--LEU-901 DEL; POLYMORPHISM; TISSUE SPECIFICITY;

Disclaimer: Any medical or genetic information present in this entry is provided for research, educational and informational purposes only. They are not in any way intended to be used as a substitute for professional medical advice, diagnostic, treatment or care.